Mayo researchers invent targeted imaging probe to aid early Alzheimer's diagnosis

04/30/04

ROCHESTER, Minn. -- Mayo Clinic researchers have devised a way to produce enhanced MRI (magnetic resonance imaging) pictures of the destructive brain lesions that cause Alzheimer's disease. This advance using laboratory mice lays the foundation for the first imaging-based diagnostic test for living Alzheimer's disease patients.

The new technique is currently used only with specially-bred laboratory animals, but is expected to move to human trials if these early results are sustained. The findings will appear in the May 25th issue of the journal Biochemistry, No. 20, vol. 43, and are online now at: http://pubs.acs.org/journals/bichaw/index.html.

"We are encouraged by these results because they suggest we are close to developing an Alzheimer's disease diagnostic tool people have been waiting on for decades," says Mayo Clinic neurology researcher and principal investigator, Joseph Poduslo, Ph.D. "A simple MRI evaluation for Alzheimer's disease would ease the suffering of so many families, and hopefully, vastly improve patient-care options." Significance of the Mayo Clinic Research

The Mayo Clinic researchers have invented a nontoxic molecular probe with three desirable traits. One, it can "home in" and target the brain regions that contain the lesions known as amyloid plaques. Second, the probe's novel chemical profile enables it to cross the blood-brain barrier to reach the plaques. This barrier normally keeps blood and other body fluids from reaching the brain. Third, and the chief goal of the experiment, the probe supplies a visual contrast chemical needed to produce high-resolution MRI images in the brains of live mice -- and ultimately, in humans.

If continued testing goes well, this procedure would enable physicians to obtain an early diagnosis in living patients, and to easily follow the progression of the disease. Currently, definitive diagnosis of Alzheimer's is made only on the basis of finding amyloid plaques during autopsy. Most Alzheimer's patients are tentatively diagnosed with the disease on the basis of behavioral evaluations.

The probe also may be used to evaluate the effectiveness of new Alzheimer's therapies that are now being designed to retard the development of the destructive brain lesions that are the hallmark of the disease. Amyloid plaques are abnormal buildups of proteins that interfere with brain communication and produce typical Alzheimer's symptoms. These include: deep and chronic forgetfulness, and loss of awareness.

The Experiment

The Mayo Clinic research team of neurologists, neuroscientists, biochemists and peptide synthesis specialists designed a derivative of the human amyloid-beta peptide (the molecule that contributes to plaque formation) to create a new kind of molecular probe. To test its targeting ability to find amyloid plaques in laboratory Alzheimer's disease mice, the researchers injected the probe it into the bloodstreams of the living mice.

The probe demonstrated the strong ability to bind to amyloid plaques in mice, increased permeability at the blood-brain barrier, and contrast enhancement in MRI scans.

Researchers also tested the probe in laboratory specimens of human Alzheimer's brains donated by families for biomedical research. While it behaved slightly differently in human brain specimens than in living mice, the probe's ability to label plaques was encouraging.

The Next Step

Further work in animal models must be carried out before the new probe could move to human trials. Says Dr. Poduslo: "While the present work underscores the development of this contrast agent for use in Alzheimer's disease, the biotechnology reported here may provide a general procedure for enhancing delivery of other diagnostic and therapeutic proteins across the blood-brain barrier for other neurodegenerative disorders as well."

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Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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